Benefit or Problem: Exploration of How Response Options Affect Self-Reported Behaviors and Interests in Autistic Adults.

Assessment of restricted, repetitive behaviors (RRB) in autism evaluations often assumes that these behaviors negatively impact the individual. Qualitative studies of first-person accounts indicate the negative impact of the stigma associated with RRBs but also provide insights into the positive aspects. The current study explores how framing response options as negative (i.e., level of problem associated with occurrence) or positive (i.e., level of benefit associated with occurrence) affects RRB self-reports in autistic adults. Sixty-six autistic adults aged 18-59 filled out the Repetitive Behavior Scale-Revised (RBS-R) and a modified RBS-R+, assessing problems and benefits of reported behaviors, respectively. There was a moderate to strong correlation between the forms, each assessing problems and benefits in terms of the number of behaviors endorsed (r = 0.746) and the levels of benefits and problems (r = 0.637). Autistic adults reported a higher number of RRBs in the form that assessed problems, but the number of behaviors was comparable between the forms when counting in the response option of the occurrence of behavior without having a benefit. Despite some variability in the level of problems and the benefits across the subdomains of RRB, autistic adults largely rated comparable levels of associated benefits and problems, highlighting the complexity of RRBs as having both positive and negative impacts. Future screening and diagnostic tools for adults should aim to assess both positive and negative aspects of autistic features to afford a more nuanced understanding of individual experiences while still yielding diagnostically relevant information. Qualitative studies are needed to better understand the complex experiences associated with these behaviors; however, it may be important to ensure that options for endorsement of behaviors without a specific benefit are also needed to ensure some behaviors (e.g., self-injurious behaviors) are not missed.

Tuning Electrocatalytic Oxygen Reduction Reaction with Dynamic Control of Electrochemical Interfaces.

Herein, we report the tuning of the activity and selectivity of the oxygen reduction reaction (ORR) through the dynamic regulation of the electrochemical interfaces to surpass the performance of conventional electrocatalysis. This is achieved by applying an oscillating potential between the ORR operating potential and anion adsorbing potential on a gold electrode. Oscillating potential enhances the selectivity for H2O2 by up to 1.35 times compared to the static potential, as confirmed by rotating ring-disk electrode and fluorescence assay measurements. We showed that the enhanced selectivity depends on dynamic adsorption and desorption of anions, and the enhancement occurs in the millisecond time scale or shorter. The transient selectivity to H2O2 can reach ∼97% within the first 5 ms after potential switching. Our results suggest that the dynamic interface can create a transient but unique microenvironment for new reactivity that cannot be reproduced under static conditions, which offers a new dimension in controlling electrocatalysis.

Comparison of Enlarged Perivascular Spaces in Early-Onset and Late-Onset Alzheimer Disease-related Cognitive Impairment: A Single Clinic-based Study in South Korea.

We examined whether there were differences in the presence of centrum semiovale-enlarged perivascular spaces (CSO-ePVS) and basal ganglia-ePVS (BG-ePVS) among patients with Alzheimer disease-related cognitive impairment (ADCI) based on their age of onset. Out of a total of 239 patients with cognitive impairment, 155 with positive amyloid-PET results were included. Among these, 43 had early-onset ADCI (EOADCI) and 112 had late-onset ADCI (LOADCI). Patients with LOADCI exhibited a higher prevalence of hypertension, lacunes, white matter hyperintensities, and BG-ePVS than those with EOADCI. BG-ePVS showed a significant correlation with age at the onset and the number of lacunes, whereas CSO-ePVS did not exhibit any association. The higher prevalence of BG-ePVS in patients with LOADCI might be attributable to vascular risk factors (hypertension) and cerebral small vessel disease (CSVD). These findings support the hypothesis that BG-ePVS is associated with CSVD and vascular risk factors, whereas CSO-ePVS is associated with cerebral amyloid angiopathy.

Cutaneous nerve distribution around first extensor compartment of the wrist: Clinical implications for ultrasound-guided injections.

Purpose: To evaluate the course of the cutaneous nerve regarding the first extensor compartment to determine whether the dorsal or volar approach is safer for local injection into the first extensor compartment guided by ultrasound. Methods: We dissected the radial side of the wrists from 28 cadavers (52 wrists). Four-points along the imaginary line were set: the styloid process and 1 cm, 2 cm, and 3 cm proximal to the styloid process. The numbers of superficial radial nerve (SRN) and lateral antebrachial cutaneous nerve (LACN) branches were counted, and distances from the imaginary line at these points and nerve diameters were recorded. Digital images were superimposed to observe overall distribution of cutaneous nerve. Results: There were means of 3.3 SRN and 0.9 LACN branches observed in each wrist. The mean number of both SRN and LACN branches was 2.3 on the dorsal side and 1.9 on the volar side. The superimposed images indicated that both the dorsal and volar sides comprised abundant cutaneous nerves and that their paths varied markedly between patients. However, we observed that larger nerves with meaningful diameters were more abundant on the dorsal than the volar side. Conclusion: There were similar numbers of cutaneous nerves on both the dorsal and volar sides; however, we observed greater abundance of thicker cutaneous nerves on the dorsal side, and these were closer to the reference line than on the volar side. This anatomical study suggests that the risk imposed to cutaneous nerves would therefore be reduced when injection on the volar side.

Unraveling the molecular mechanisms of cell migration impairment and apoptosis associated with steroid sulfatase deficiency: Implications for X-linked ichthyosis.

Steroid sulfatase (STS) deficiency is responsible for X-linked ichthyosis (XLI), a genetic disorder characterized by rough and dry skin caused by excessive keratinization. The impaired keratinization process leads to reduced cell mobility and increased apoptosis, which can cause an excessive buildup of the stratum corneum. In this study, we investigated the mechanisms underlying XLI and found that STS deficiency reduces cell mobility and increases apoptosis in human keratinocyte HaCaT cells. To explore these mechanisms further, RNA-sequencing was conducted on skin tissues from STS transgenic and knockout mice. Our RNA-seq results revealed that STS deficiency plays a critical role in regulating multiple signaling pathways associated with cell mobility and apoptosis, such as Wnt/ß signaling and the Hippo signaling pathway. Knockdown of the STS gene using shRNA in HaCaT cells led to an upregulation of E-cadherin expression and suppression of key factors involved in epithelial-mesenchymal transition (EMT), such as N-cadherin and vimentin. Inhibition of EMT involved the Hippo signaling pathway and reduction of HIF-1α. Interestingly, inhibiting STS with shRNA increased mitochondrial respiration levels, as demonstrated by the extracellular flux oxygen consumption rate. Additionally, we observed a significant increase in ROS production in partial STS knockout cells compared to control cells. Our study demonstrated that the excessive generation of ROS caused by STS deficiency induces the expression of Bax and Bak, leading to the release of cytochrome c and subsequent cell death. Consequently, STS deficiency impairs cell mobility and promotes apoptosis, offering insights into the pathophysiological processes and potential therapeutic targets for XLI.

Anatomical Relationship between the Inferior Temporal Septum and the Temporal Branch of the Facial Nerve for Clinical Applications.

BACKGROUND: The inferior temporal septum (ITS) is a fibrous adhesion between the superficial temporal fascia and the superficial layer of the deep temporal fascia. This study identified detailed the anatomical relationship between the ITS and the temporal branch of the facial nerve (TBFN) for facial nerve preservation during temple interventions. METHODS: Among 33 Korean cadavers, 43 sides of TBFNs in temporal regions were dissected after identifying the ITS between the superficial temporal fascia and superficial layer of the deep temporal fascia through blunt dissection. The topography of the ITS and TBFN were investigated with reference to several facial landmarks. Regional relationships with the ITS and TBFN within the temporal fascial layers were histologically defined from five specimens. RESULTS: At the level of the inferior orbital margin by the tragion, the mean distances from the lateral canthus to the anterior and posterior branches of the TBFN were 5 and 6.2 cm, respectively. At the lateral canthus level, the mean distance from the lateral canthus to the posterior branch of the TBFN was similar to that to the ITS, at 5.5 cm. At the superior orbital margin level, the posterior branch of the TBFN ran cranial to the ITS adjacent to the frontotemporal region. The TBFN ran through the subsuperficial temporal fascia layer and the nerve fibers located cranially, and within the ITS meshwork in the upper temporal compartment. CONCLUSION: The area of caution during superficial temporal fascia interventions related to the TBFN was clearly identified in the upper temporal compartment, which is known to lack important structures.

ANKS1A regulates LDL receptor-related protein 1 (LRP1)-mediated cerebrovascular clearance in brain endothelial cells.

Brain endothelial LDL receptor-related protein 1 (LRP1) is involved in the clearance of Aß peptides across the blood-brain barrier (BBB). Here we show that endothelial deficiency of ankyrin repeat and SAM domain containing 1 A (ANKS1A) reduces both the cell surface levels of LRP1 and the Aß clearance across the BBB. Association of ANKS1A with the NPXY motifs of LRP1 facilitates the transport of LRP1 from the endoplasmic reticulum toward the cell surface. ANKS1A deficiency in an Alzheimer's disease mouse model results in exacerbated Aß pathology followed by cognitive impairments. These deficits are reversible by gene therapy with brain endothelial-specific ANKS1A. In addition, human induced pluripotent stem cell-derived BBBs (iBBBs) were generated from endothelial cells lacking ANKS1A or carrying the rs6930932 variant. Those iBBBs exhibit both reduced cell surface LRP1 and impaired Aß clearance. Thus, our findings demonstrate that ANKS1A regulates LRP1-mediated Aß clearance across the BBB.

YPEL3 expression induces cellular senescence via the Hippo signaling pathway in human breast cancer cells.

The Hippo pathway is a signaling pathway that controls organ size in animals by regulating cell proliferation and apoptosis. Yes-associated protein 1 (YAP1), an oncogene associated with the development and progression of breast cancer, is downregulated by the Hippo pathway and is associated with the development and progression of breast cancer. Yippee-like 3 (YPEL3) is a target gene of the tumor suppressor protein p53, and its activation has been shown to inhibit cell growth, induce cellular senescence, and suppress tumor cell metastasis. In this study, we found that YAP1 inhibits the expression of YPEL3 expression in breast cancer cells. Furthermore, a decrease in lamin B1, a marker protein of cellular senescence, coupled with the activation of senescence-associated ß-galactosidase indicated that upregulating YPEL3 levels through YAP1 downregulation can induce cellular senescence. Additionally, elevated YPEL3 levels resulted in higher levels of oxygen consumption rate in mitochondria, thus promoting apoptosis. This suggests that YPEL3 plays a crucial role in regulating oxidative stress and cell apoptosis in breast cancer cells. Therefore, the interaction between YAP1 and YPEL3 represents a novel mechanism of cellular senescence mediated by the Hippo signaling pathway. Collectively, our findings suggest that the Hippo signaling pathway plays an important role in regulating cellular senescence, which could have implications for the development of new therapeutic strategies for diseases such as cancer.

ApoE4-dependent lysosomal cholesterol accumulation impairs mitochondrial homeostasis and oxidative phosphorylation in human astrocytes.

Recent developments in genome sequencing have expanded the knowledge of genetic factors associated with late-onset Alzheimer's disease (AD). Among them, genetic variant ε4 of the APOE gene (APOE4) confers the greatest disease risk. Dysregulated glucose metabolism is an early pathological feature of AD. Using isogenic ApoE3 and ApoE4 astrocytes derived from human induced pluripotent stem cells, we find that ApoE4 increases glycolytic activity but impairs mitochondrial respiration in astrocytes. Ultrastructural and autophagy flux analyses show that ApoE4-induced cholesterol accumulation impairs lysosome-dependent removal of damaged mitochondria. Acute treatment with cholesterol-depleting agents restores autophagic activity, mitochondrial dynamics, and associated proteomes, and extended treatment rescues mitochondrial respiration in ApoE4 astrocytes. Taken together, our study provides a direct link between ApoE4-induced lysosomal cholesterol accumulation and abnormal oxidative phosphorylation.

Galvanic Bipolar Electrode Arrays with Self-Driven Optical Readouts.

In this work, we report a bipolar electrode (BPE) array system with self-driven optical readouts of the faradic current flowing through the BPEs. The BPE array system is based on the spontaneous redox reactions that are respectively occurring at opposite poles of the BPEs with appropriate electrocatalysts on the poles; this system is analogous to one consisting of galvanic electrochemical cells. The galvanic BPE array system operates in a self-powered mode that requires there to be neither a direct electrical connection nor external electrical polarization to each BPE. Importantly, the appropriate electrocatalysts on the poles play a critical role in the galvanic BPE array system to induce the spontaneous redox reactions occurring at the poles of BPEs. Moreover, the galvanic BPE array system provides self-driven optical readouts, including fluorometric and colorimetric ones, to report the faradaic current resulting from the spontaneous redox reactions on the BPE poles. Based on the unique benefits that the galvanic BPE array system has over conventional BPEs, we demonstrated the promising potential of galvanic BPE arrays for the simple yet rapid and quantitative screening of electrocatalysts for the oxygen reduction reaction as well as sensitive sensing of H2O2 in parallel.

Food Additive Solvents Increase the Dispersion, Solubility, and Cytotoxicity of ZnO Nanoparticles.

Zinc oxide (ZnO) nanoparticles (NPs) are utilized as a zinc (Zn) fortifier in processed foods where diverse food additives can be present. Among them, additive solvents may strongly interact with ZnO NPs by changing the dispersion stability in food matrices, which may affect physico-chemical and dissolution properties as well as the cytotoxicity of ZnO NPs. In this study, ZnO NP interactions with representative additive solvents (methanol, glycerin, and propylene glycol) were investigated by measuring the hydrodynamic diameters, solubility, and crystallinity of ZnO NPs. The effects of these interactions on cytotoxicity, cellular uptake, and intestinal transport were also evaluated in human intestinal cells and using in vitro human intestinal transport models. The results revealed that the hydrodynamic diameters of ZnO NPs in glycerin or propylene glycol, but not in methanol, were significantly reduced, which is probably related to their high dispersion and increased solubility under these conditions. These interactions also caused high cell proliferation inhibition, membrane damage, reactive oxygen (ROS) generation, cellular uptake, and intestinal transport. However, the crystal structure of ZnO NPs was not affected by the presence of additive solvents. These findings suggest that the interactions between ZnO NPs and additive solvents could increase the dispersion and solubility of ZnO NPs, consequently leading to small hydrodynamic diameters and different biological responses.

Nanoelectrochemistry in electrochemical phase transition reactions.

Electrochemical phase transition is important in a range of processes, including gas generation in fuel cells and electrolyzers, as well as in electrodeposition in battery and metal production. Nucleation is the first step in these phase transition reactions. A deep understanding of the kinetics, and mechanism of the nucleation and the structure of the nuclei and nucleation sites is fundamentally important. In this perspective, theories and methods for studying electrochemical nucleation are briefly reviewed, with an emphasis on nanoelectrochemistry and single-entity electrochemistry approaches. Perspectives on open questions and potential future approaches are also discussed.

SUMO enhances unfolding of SUMO-polyubiquitin-modified substrates by the Ufd1/Npl4/Cdc48 complex.

The Ufd1/Npl4/Cdc48 complex is a universal protein segregase that plays key roles in eukaryotic cellular processes. Its functions orchestrating the clearance or removal of polyubiquitylated targets are established; however, prior studies suggest that the complex also targets substrates modified by the ubiquitin-like protein SUMO. Here, we show that interactions between Ufd1 and SUMO enhance unfolding of substrates modified by SUMO-polyubiquitin hybrid chains by the budding yeast Ufd1/Npl4/Cdc48 complex compared to substrates modified by polyubiquitin chains, a difference that is accentuated when the complex has a choice between these substrates. Incubating Ufd1/Npl4/Cdc48 with a substrate modified by a SUMO-polyubiquitin hybrid chain produced a series of single-particle cryo-EM structures that reveal features of interactions between Ufd1/Npl4/Cdc48 and ubiquitin prior to and during unfolding of ubiquitin. These results are consistent with cellular functions for SUMO and ubiquitin modifications and support a physical model wherein Ufd1/Npl4/Cdc48, SUMO, and ubiquitin conjugation pathways converge to promote clearance of proteins modified with SUMO and polyubiquitin.

In Situ Confocal Fluorescence Lifetime Imaging of Nanopore Electrode Arrays with Redox Active Fluorogenic Amplex Red.

Direct imaging of electrochemical processes on electrode surfaces is a central part of understanding spatially heterogeneous electrochemical processes on the surfaces. Herein, we report a strategy for the spatially resolved imaging of local faradaic processes on nanoscale electrochemical interfaces. This strategy is based on fluorescence lifetime imaging microscopy (FLIM) with the use of Amplex Red as a fluorogenic redox probe. After verifying the capability of Amplex Red for fluorescence lifetime imaging, we demonstrated the turn-on FLIM-based imaging of faradaic processes on the electrochemical interfaces of different dimensions. In particular, we achieved spatially resolved visualization of the local electrochemical processes occurring on even nanopore electrode arrays as well as conventional microelectrodes, including disk-shaped ultramicroelectrodes and interdigitated array microelectrodes.

Functional Characterization of Drosophila melanogaster CYP6A8 Fatty Acid Hydroxylase.

Genomic analysis indicated that the genome of Drosophila melanogaster contains more than 80 cytochrome P450 genes. To date, the enzymatic activity of these P450s has not been extensively studied. Here, the biochemical properties of CYP6A8 were characterized. CYP6A8 was cloned into the pCW vector, and its recombinant enzyme was expressed in Escherichia coli and purified using Ni2+-nitrilotriacetate affinity chromatography. Its expression level was approximately 130 nmol per liter of culture. Purified CYP6A8 exhibited a low-spin state in the absolute spectra of the ferric forms. Binding titration analysis indicated that lauric acid and capric acid produced type І spectral changes, with Kd values 28 ± 4 and 144 ± 20 µM, respectively. Ultra-performance liquid chromatography-mass spectrometry analysis showed that the oxidation reaction of lauric acid produced (ω-1)-hydroxylated lauric acid as a major product and ω-hydroxy-lauric acid as a minor product. Steady-state kinetic analysis of lauric acid hydroxylation yielded a kcat value of 0.038 ± 0.002 min-1 and a Km value of 10 ± 2 µM. In addition, capric acid hydroxylation of CYP6A8 yielded kinetic parameters with a kcat value of 0.135 ± 0.007 min-1 and a Km value of 21 ± 4 µM. Because of the importance of various lipids as carbon sources, the metabolic analysis of fatty acids using CYP6A8 in this study can provide an understanding of the biochemical roles of P450 enzymes in many insects, including Drosophila melanogaster.

Abdominal Wall Block Decreases Intraoperative Opioid Con-Sumption by Surgical Pleth Index-Guided Remifentanil Administration in Single-Port Laparoscopic Herniorrhaphy: A Prospective Randomized Controlled Trial.

Abdominal wall blocks (AWBs) can reduce pain during surgery and lessen opioid demand. Since it is difficult to know the exact level of intraoperative pain, it is not known how much the opioid dose should be reduced. In this study, using the surgical pleth index (SPI), which indicates pain index from sympathetic fibers, the amount of remifentanil consumption was investigated. We conducted single-port laparoscopic hernia repair in 64 patients, as follows: the regional block group (R group) was treated with AWB, while the control group (C group) was only subjected to general anesthesia. In both groups, the remifentanil concentration was adjusted to maintain the SPI score between 30 and 40 during surgery. The primary parameter was the amount of remifentanil. A total of 52 patients completed the study (24 in the R group, 28 in the C group). The remifentanil dose during surgery was decreased in the R group (29 ± 21 vs. 56 ± 36 ng/kg/min; p = 0.002). Visual analogue scale score and additional administrated analgesics were also low in the R group. As such, AWB can reduce the remifentanil dose while maintaining the same pain level.

Are There Other Muscle Fibers on the Orbicularis Oris Muscle in the Upper Lip?

BACKGROUND: The elevator muscles of the upper lip are the levator labii superioris alaeque nasi, levator labii superioris, and zygomaticus minor muscles, which function by means of their insertions into the skin of the upper lip. However, many textbooks and journal articles state that no muscle fibers are present on the orbicularis oris muscle in the upper lip. The authors attempted to determine whether there is a superficial muscle layer in addition to the orbicularis oris muscle in the upper lip. METHODS: The authors performed gross dissections of 10 formalin-fixed cadavers and applied micro-computed tomography to six formalin-fixed cadavers. The fine dissection of the upper lip was performed in a layer-by-layer manner that elucidated its muscle layers. The entire layer of the upper lip was separated and pretreated with phosphotungstic acid for micro-computed tomography. The samples used for micro-computed tomography were repurposed for use in histologic analysis. An ultrasonography study was also performed. RESULTS: The presence of a muscle layer on the orbicularis oris muscle was confirmed in all samples. The elevator muscle fibers of the upper lip formed a layer by combining with connective tissue. Micro-computed tomography indicated lower terminal insertions of the elevator muscles throughout the upper lip. All parts of the upper lip skin were inserted into the orbicularis oris muscle. The histologic findings were similar to those of micro-computed tomography. CONCLUSION: The authors' findings could be used to improve aesthetic and surgical procedures performed on the upper lip, such as correction of gummy smile and transverse upper labial crease, or postresection reconstruction of the upper lip.

Activation of the SigE-SigB signaling pathway by inhibition of the respiratory electron transport chain and its effect on rifampicin resistance in Mycobacterium smegmatis.

Using a mutant of Mycobacterium smegmatis lacking the major aa3 cytochrome c oxidase of the electron transport chain (Δaa3), we demonstrated that inhibition of the respiratory electron transport chain led to an increase in antibiotic resistance of M. smegmatis to isoniazid, rifampicin, ethambutol, and tetracycline. The alternative sigma factors SigB and SigE were shown to be involved in an increase in rifampicin resistance of M. smegmatis induced under respiration-inhibitory conditions. As in Mycobacterium tuberculosis, SigE and SigB form a hierarchical regulatory pathway in M. smegmatis through SigE-dependent transcription of sigB. Expression of sigB and sigE was demonstrated to increase in the Δaa3 mutant, leading to upregulation of the SigB-dependent genes in the mutant. The pho U2 (MSMEG_1605) gene implicated in a phosphate-signaling pathway and the MSMEG_1097 gene encoding a putative glycosyltransferase were identified to be involved in the SigB-dependent enhancement of rifampicin resistance observed for the Δaa3 mutant of M. smegmatis. The significance of this study is that the direct link between the functionality of the respiratory electron transport chain and antibiotic resistance in mycobacteria was demonstrated for the first time using an electron transport chain mutant rather than inhibitors of electron transport chain.

Learning from the Heterogeneity at Electrochemical Interfaces.

Understanding the structure-activity relationship at electrochemical interfaces is crucial in improving the performance of practical electrochemical devices, ranging from fuel cells, electrolyzers, and batteries to electrochemical sensors. However, functional electrochemical interfaces are often complex and contain various surface structures, creating heterogeneity in electrochemical activity. In this Perspective, we highlight the role of heterogeneity in electrochemistry, especially in the context of electrocatalysis. Current methods for revealing the heterogeneity at electrochemical interfaces, including nanoelectrochemistry tools and single-entity approaches, are discussed. Lastly, we provide perspectives on what one can learn by studying heterogeneity and how one can use heterogeneity to design more efficient electrochemical devices.